Almost half of the Dutch population is currently characterized by overweight and obesity. Losing weight is not the problem in obesity treatment, it is the seemingly obligatory weight regain after weight loss: the yoyo-effect. The primary objective of this study is to investigate the association between the weight-loss-induced cellular stress response and the rate of weight regain. The secondary objective is to investigate the differences in cellular stress response and weight regain after rapid and slow weight loss. To investigate this, subjects will receive meal replacements replacing either all or part of the daily meals during the intervention period. THe first group will consume 500 kcal/d diet for 5 weeks while the second group consumes a 1250 kcal/d diet for 3 months, both followed by 1 week normalization and a 2 week strict weight maintenance diet. During the 9-month follow-up period subjects will receive dietary advice according to the Dutch recommendations for healthy eating. The association between the amount of weight regain after the weight loss period and changes in adipokines, parameters of adipocyte metabolism, in vivo adipose tissue metabolism, adipocyte extracellular matrix gene expression profiles, adipocyte stress protein expression and gene polymorphisms in selected genes.

change in the adipocyte extracellular matrix gene and protein expression profile due to dietary intervention (VLCD-group) [ Time Frame: at baseline and after 5 weeks of VLCD diet ] [ Designated as safety issue: No ]

VLCD diet group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile during weight-stable period (VLCD-group) [ Time Frame: after 5 weeks of VLCD diet and at 9 weeks ] [ Designated as safety issue: No ]

VLCD diet group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile during follow-up period (VLCD-group) [ Time Frame: at 9 weeks and after follow-up period at 46 weeks ] [ Designated as safety issue: No ]

VLCD diet group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile due to dietary intervention (LCD-group) [ Time Frame: at baseline and after 12 weeks of LCD diet ] [ Designated as safety issue: No ]

LCD diet group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile during weight-stable period (LCD-group) [ Time Frame: after 12 weeks of LCD diet and at 16 weeks ] [ Designated as safety issue: No ]

LCD diet group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile during follow-up period (LCD-group) [ Time Frame: at 16 weeks and after follow-up period ] [ Designated as safety issue: No ]

LCD diet group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile in the LCD-group compared to the VLCD-group [ Time Frame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks ] [ Designated as safety issue: No ]

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in the adipocyte extracellular matrix gene and protein expression profile in relation to weight regain during follow-up [ Time Frame: at baseline, at 5, 9, 12, 16, 46 and 53 weeks ] [ Designated as safety issue: No ]

In LCD-group and VLCD-group

Adipocyte extracellular matrix gene expression profile assessed:

micro-arrays on RNA expression

protein expression

Genetic polymorphisms: focus on polymorphisms in genes (a) that are preferentially expressed in white adipose tissue like TIMP4, (b) that have a proposed anchoring role of the cells to the basal lamina like the non-fibrillar type collagens IV and VI, (c) that are essential for adipose tissue development like MMP14, and (d) for which association has been found with obesity or adiposity like TIMP1, MMP2 and MMP9

change in adipocyte stress proteins expression due to dietary intervention (VLCD-group) [ Time Frame: at baseline and after 5 weeks of VLCD diet ] [ Designated as safety issue: No ]

planned major changes in physical activity during the study to an extent that might interfere with the study outcome as judged by the investigator;

blood donation within the past 2 months prior to the study

weight change of >3 kg within 2 months prior to the study

psychiatric disease (based on medical history only)

pregnant or lactating women, or women planning to become pregnant within the next 12 months

surgically treated obesity

participation in other clinical studies within the last 3 months

drug abuse (based on clinical judgment)

unable to give informed consent

unable to engage in a low-calorie diet

unable to lose more then 8% of body weight after weight-loss period

following a special diet (vegetarian, Atkins or other).

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559415

Locations

Netherlands

Maastricht University

Maastricht, Limburg, Netherlands, 6200 MD

Sponsors and Collaborators

Maastricht University Medical Center

ZonMw: The Netherlands Organisation for Health Research and Development